Manufacture of substituted malonic esters



Patented Mar. 22, 1938 v UNITED STATES PATENT OFFICE MANUFACTURE OF SUBSTITUTED MALONIC ESTERS John David Kendall, moi-d, England, alsis or to Illord Limited, Ill'ord, Essex, England, a British company No Drawing. Application May 18, 1936, Serial No. 80,461. In Great Britain May 25, 1935 13 Claims.

by reacting l-acetanilido-vinyl benzthiazole and diethyl malonate in the presence of pyridine, and it is indicated that this compound has sensitizing properties for photographic silver chloride emulsions.

It has now been found that other analogous meso-substltuted malonic esters may be produced and that these esters are sensitizers for silver chloride and other silver halide photographic emulsions, and it is an object of the present invention to produce a series of such meso-substituted malonic esters typified by the above example. The main distinction of the process of the present invention from the process described in the specifications of British Patent No. 431,141 resides in the fact that instead of using an unsubstituted malonic ester such as diethyl malonate as one of the starting materials, a meso-substituted malonic ester is employed.

According to the present invention a process for the production of mesa-substituted malonic esters comprises reacting in the presence of an acid binding substance, such as pyridine, or a strong base such as sodium ethoxide one molecular proportion of a quaternary salt 01 a heterocyclic nitrogen compound having a reactive methyl group with one molecular proportion of a mew-substituted malonic ester in which the substituent group is one of the following: hydroxymethylene, alkoxymethylene, arylaminomethylene, acylarylaminomethylene and, aminomethylene.

It is believed that the quaternary salt reacts with the substituted malonic ester in the manner shown by the following equation, in which Y represents the remainder of the heterocyclic nitrogen compound, R represents an alkyl group and X represents an acid radical:

- coon +mon The ethoxymethylene malonic ester given in the above general equation is one of the most convenient mesa-substituted malonic esters which may be employed in the process of the present invention, but other alkoxy methylene malonic esters may be employed, and also malonic esters having other substituent groups, for example hydroxymethylene malonic ester, arylaminomethylene malonic ester, e. g. anilido-methylene malonic ester, acylarylamino-methylene malonic ester. e. g. acetanilido methylene malonic ester, and aminomethylene malonic ester. The preparation of malonic esters containing as a mesa-substituent anarylaminomethylene, an acylarylaminomethylene or an aminomethylene group is described in a paper by Claisen in Annalen volume 297, page 76 et seq.

Quaternary salts of any of the heterocyclic nitrogen compounds which are normally employed in the preparation of cyanine dyes may be employed in carrying out the process of the present invention, for example thiazoles, oxazoles, quinolines, selenazoles, quinazolines, dia- :-v

zines, pyridiminesand their homologues and substituent derivatives, including the corresponding benzand naphtho-compounds.

As already indicated the meso-substituted malonic esters obtained in accordance with the present invention are sensitizers for photographic silver halide emulsions, and one or more of the compounds may be incorporated in a photographic silver halide emulsion, in accordance with known practice, either by mixing with the emulsion before it is coated on a support or by bathing the coated support in a solution of the compound.

Several specific examples of the process of the present invention are given below by way of example only in order to illustrate the invention.

meme I Preparation of 1.as-trimnwianeoz zieinez-etm glidene malonic-diethul-ester 5 30 gms. oi trimethylindolenine methiodide, 25 gms. oi! ethoxymethylene-malonic ester and 100 ccs. oi pyridine were heated together under a refiux condenser for one hour and the mixture was then poured into 1 litre oi! water. A yellow dye separated out, and was filtered ofl, washed and recrystallized from methyl alcohol to give yellow crystals.

CHI

COOEt COOEt COOEt N ooont+nton Emu: II

Preparation of z-ethyl dihudro-benzthiazolyltame-1-eth1llidene-malonic-diethyl-ester 30.5 ms. of l-methyl-benzthiazole-ethiodide,

25 ms. of ethoxymethylene-malonic-diethylester and 120 ccs. of pyridine were mixed together and heated under a reflux condenser for one hour.

The mixture was then poured into 1 litre of water when a yellow dye separated out. This was collected, washed and recrystallized from benzene to give pale yellow needles of a dyestufl similar to that from the condensation of l-acetanilidovinylbenzthiazole-ethiodide with diethyl-malonate.

COOEt coon: c=oncn=c +111 N coonwmon Exmru III Preparation of N-methyl-dihydro-benzthiazolylidine Z-ethylidene malom'c ethyl ester Exmu: IV

Preparation of N-methyl-dihudro-benzomazolylidine Z-ethylidene malom'c ethyl ester 13.3 gms. of l-methylbenzoxazole were heated together with 18.6 gms. oi methyl-p-toluene sulphonate for 2% hours at -150" C.- 21.6 gms. of ethoxymethylene malonic ester and 60 cos. of pyridine were then added and the mixture boiled gently 'for a further 50 minutes. was then poured into water and the precipitate formed was extracted with benzene and recrystallized from spirit to form long light yellow needles melting at C.

Exmu: V

N-methuldihydroquinolulidene-2-ethylidene-malonic-diethul-ester 20 guns. of quinaldlne were heated with 26 gm. of methyl-p-toluene sulphonate for four hours at 120-130 C.

31 gms. of ethoiwmethylene-malonic-diethylester were then added together with 100 ccs. pyridine and the mixture was boiled for about fortyfive minutes.

The liquor was then diluted with a large bulk of water and allowed to stand. Green crystals separated out and were dissolved in hot benzene and filtered from a small quantity of insoluble matter. On concentration oi the solution and cooling, the dye separated out as large brown rhomboids (melting point 123 C.) which were soluble in ether, alcohol and benzene to give a deep orange yellow solution.

Exmu: VI

N-methyldihudroquinolylidene-4-ethylidene-ma:- lonic-diethyl-ester 28.5 gms. lepidine methyl iodide and 21.6 gms. etho'xymethylene malonic diethyi ester were mixed with 100 ccs. pyridine and heated for about 20 minutes. The solution obtained was diluted with water and the pyridine neutralized by the addition of acetic acid when the dyestufl was deposited as deep red brown crystals melting at 210 C. and soluble in the usual organic solvents to give a magenta coloured solution.

Exmu VlI N methyldihydropyridylidene 2 ethylidenemalonic-diethyl-ester was obtained by condensing one molecular proportion of a-picolinemethosulphate and one molecular proportion of ethoxymethylene-malonic-diethyl-ester in the presence of one molecular proportion of sodium. ethoxide in alcoholic solution. The dye was a yellow solid giving bright yellow solutions in the usual organic solvent.

Exams: VIII 3-N -methylidihydroquinazolylidine 4 ethylidene-malonic-diethyl-ester was obtained by heating 4-methyl-quinazolinemetho-p-toluene sulphonate with ethoxymethylene-malonic-diethylester in the presence of pyridine. The dye gave yellow solutions.

EXAMPLE 1X N-methyl-3:4-benzdihydrobenzthiazolylidene- 1-ethylidene-malonic-diethyl-ester 19.9 gms. of 1-methyl3:4-benzbenzthiazole and 18.6 gms. of methyl-p-toluene sulphonate were heated together for five hours at -l70 C. The mixture was allowed to cool and 21.6 gms. of ethoxymethylene-malonic-diethyl-ester followed by 140 cos. of pyridine were added. The solution was heated under reflux ior forty-five minutes and was then diluted with a large bulk oi! water and the precipitate which formed was filtered oil. The slightly oily solid obtained was dissolved in hot benzene and filtered, petroleum The mixture t, ether (40-60 boiling point) was then added and the dyestuif was precipitated out as fine orange needles, 0! melting point 158-159 0., giving a bright yellow solution in organic solvents.

Exmmx 1-ethul-fi methyldihydroquinolylidene 2 emudene-malonic-diethul-ester A mixture of 31.3 gms. oi p-toluquinaldine ethiodide and 21.6 gms. of ethoxy-methylenemalonlc-diethyl-ester were heated under reflux for forty-five minutes in the presence or 150 cos. 0! pyridine. The solution was diluted with water and acetic acid added to neutralize excess pyridine. On standing red brown crystals with bluish reflex were deposited. These dissolved in organic solvents to give orange yellow solutions.

Exam XI N-methyl- 3:4 benzdihydrobenzozazolylidene-1 ethylidene-malo'nic-ester Amixture of 33.9 gms. of 2-methyl-p-naphthoxazole ethiodide, 21.6 ms. of ethoxymethylenemalonic-diethyl-ester, and 200 ccs. pyridine were boiled under reflux for thirty minutes. The solution on dilution with water and addition of acetic acid to neutralize the pyrldinedeposited a yellow oil which rapidly hardened. On crystallization from benzene yellow crystals were obtained which dissolved in organic solvents to give lemon yellow solutions.

Exanrm XII N-methz l-dihudrobenzselenazolylidene- 1 -ethylidene-malonic-diethyl-ester 19.6 gms. of l-methylbenrselenazole and 18.6 gms. of methyl-p-toluene sulphonate were mixed in a 500 ccs. bolthead flask and heated together for four hours at -150 C. After cooling 21.6 gms. of ethoxymethylene-malonic-diethyl-ester and 120 ccs. pyridine were added and the. mixture heated under reflux for forty-five minutes. On dilution a solid was deposited which was illtered at the pump and crystallized by solution in hot benzene, filtered hot from insoluble material and allowed to cool. The dye obtained dissolved in organic solvents to give bright yellow solutions.

Exam X111 1 :3 :3-trimethylindolylidene-2-ethylidene malonic-diethyl-ester -methylene-malonic-diethyl-ester at -160 C.

for two hours. The mixture was dissolved-up in alcohol and reprecipitated with water, and the.

above dyestufl was obtained from the semi-solid precipitate by extraction with ether.

The same product was also obtained in a similar manner employing anilido-methyiene-malonic diethyl-ester in place of the amino-methylenediethyl-malonic-ester.

employed as the acid binding substance.

3. The process 01 claim 1 wherein an alcohol is used as the solvent and a strong base is used as the acid binding substance.

4. A process for the production 01 substituted malonic esters comprising mixing an acid binding substance, one molecular proportion of a quaternary salt of a heterocycllc nitrogen compound having a reactive methyl group and substantially one molecular proportion of a mesosubstituted malonic ester in which the substituent group is one selected from the group consisting of hydroxy-methylene, alkoxy-methylene, arylamino-methylene, acyiarylamino methylene and amino-methylene, and heating the mixture under a reflux condenser until reaction has been eflected between the quaternary salt of a heteroctygclic nitrogen compound and the meso-malonic es r.

5. The process of claim 4 wherein the heating is continued for approximately one hour and the reaction mixture is then poured into water.

6. A process for the production of substituted malonic esters comprising reacting, in the presence of an acid binding substance, one molecular proportion 01 a quaternary salt of a heterocyclic nitrogen compound having a reactive methyl group with substantially one molecular proportion of an alkoxy-methylene malonic ester.

7. A process for the production of substituted malonic esters comprising reacting, in the presence of an acid binding substance,'one molecular proportion of a quaternary salt of a heterocyclic nitrogen compound having a reactive methyl group with substantially one molecular proportion of an ethoxy-methylene malonic ester.

8. A process for the production of substituted malonic esters comprising reacting, in the presence of an acid binding substance. one molecular proportion of a quaternary salt of a heterocyclic nitrogen compound having a reactive methyl group with substantially one molecular proportion of an anilido-methylene malonic ester.

9. A process for the production or 1.3.3-trimethylindolylidine-2-ethylidene malonic-diethylester consisting in reacting, in the presence of an acid binding substance, substantially equimolecular proportions of trimethylindolenine methiodide and ethoxy-methylene-malonic ester.

10. A process for the production 01 Z-ethyldihydro-benz'thiazolylidine- 1 -ethylidene-malonic-diethyl-ester consisting in reacting, in the presence of an acid binding substance, substantially equimolecular proportions of l-methylbenzthiazole-ethiodide and ethoxy-methylenemalonlc-diethyl-malonic ester.

11. A process for the production of N-methyldihydroquinolylidene-2-ethylidene malonic diethyl ester consisting in reacting, in the presence of an acid binding substance, substantially equimolecular proportions of quinaldine para-toluene sulphonate and ethoxy-methylene-malonic diethyi ester.

12. A process for the production of substituted malonic esters comprising reacting, in the presence of an acid binding substance, one molecular proportion of a quaternary salt of a heterocyclic nitrogen compound of the type used in the preparation of cyanine dyes, having a reactive methyl group with substantially one molecular proportion of a meso-substituted malonic ester in which the substituent group is one selected from the group consisting of hydroxy-methylene, alkoxy-methylene, arylamino-methylene, acylarylamino-methylene and amino-methylene.

13. A process for the production of substituted malonic esters comprising reacting, in the presence of an acid binding substance, one molecular proportion of a quaternary salt of a heterocyclic nitrogen compound of the type used in the preparation of cyanine dyes taken from the class consisting of thiazoles, oxazoles, quinolines, selenazoles, and quinazolines, having a reactive methyl group with substantially one molecular proportion of a mesa-substituted malonic ester in which the substituent group is one selected from the group consisting of hydroxy-methylene, aikoxy-methylene, arylamino-methylene, acylarylamino-methylene and amino-methylene.

JOHN DAVID KENDALL. 

